Myo-Inositol is universally distributed in nature and scyllo-inositol is found to accompany myo- whenever sufficiently sensitive methods have been used for its detection. While myo-inositol has a clearly defined function as a precursor of the phosphoinositides, it is widely held that it has other important functions also. Scyllo-Inositol has no known function. These two inositols are found in high concentration in nervous tissue. In the proposed research we plan to investigate the mechanisms of the L-myo-inositol-1-P synthase and the myo-inositol epimerase which produces scyllo-inositol. Both enzymes have been isolated from bovine brain and purification studies are underway. Also being studied is the L-myo-inositol-1-P phosphatase from bovine brain. Our primary interest in the phosphatase is in learning if it has a role in the effect exerted by lithium on inositol and inositol-1-P levels in rat brain. We are also carrying out, in collaboration with the Mayo Clinic, the measurement of fructose, sorbitol, scyllo-inositol and myo-inositol in normal and diabetic sural nerve samples. This study may provide evidence for a role of these substances in the etiology of diabetic peripheral neuropathy.